Müller cells play a critical role in retinal metabolism and are among the first cells to demonstrate metabolic changes in retinal stress or disease. The timing, extent, regulation, and impacts of these changes are not yet known. We evaluated metabolic phenotypes of Müller cells in the degenerating retina. Retinas harvested from wild-type (WT) and rhodopsin Tg P347L rabbits were fixed in mixed aldehydes and resin embedded for computational molecular phenotyping (CMP). CMP facilitates small molecule fingerprinting of every cell in the retina, allowing evaluation of metabolite levels in single cells. CMP revealed signature variations in metabolite levels across Müller cells from TgP347L retina. In brief, neighboring Müller cells demonstrated variability in taurine, glutamate, glutamine, glutathione, glutamine synthetase (GS), and CRALBP. This variability showed no correlation across metabolites, implying the changes are functionally chaotic rather than simply heterogeneous. The inability of any clustering algorithm to classify Müller cell as a single class in the TgP347L retina is a formal proof of metabolic variability in the present in degenerating retina. Although retinal degeneration is certainly the trigger, Müller cell metabolic alterations are not a coherent response to the microenvironment. And while GS is believed to be the primary enzyme responsible for the conversion of glutamate to glutamine in the retina, alternative pathways appear to be unmasked in degenerating retina. Somehow, long term remodeling involves loss of Müller cell coordination and identity, which has negative implications for therapeutic interventions that target neurons alone.
Pubmed ID: 27142256 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsThis monoclonal targets Glutamine Synthetase
View all literature mentionsThis polyclonal targets GABA (aldehyde-trapped)
View all literature mentionsThis polyclonal targets GABA (aldehyde-trapped)
View all literature mentionsThis polyclonal targets taurine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets L-glutamine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets Total glutathione (aldehyde-trapped): GSH+GSSG.
View all literature mentionsThis polyclonal targets glycine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets L-glutamate (aldehyde-trapped)
View all literature mentionsThis polyclonal targets L-glutamate (aldehyde-trapped)
View all literature mentionsThis polyclonal targets glutaraldehyde-cross-linked L-aspartate
View all literature mentionsThis polyclonal targets agmatine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets agmatine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets L-alanine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets L-alanine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets agmatine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets L-glutamate (aldehyde-trapped)
View all literature mentionsThis polyclonal targets glycine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets L-glutamine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets L-glutamate (aldehyde-trapped)
View all literature mentionsThis polyclonal targets GABA (aldehyde-trapped)
View all literature mentionsThis polyclonal targets agmatine (aldehyde-trapped)
View all literature mentionsThis polyclonal targets glutaraldehyde-cross-linked L-aspartate
View all literature mentionsThis monoclonal targets Glutamine Synthetase
View all literature mentionsThis polyclonal targets GABA (aldehyde-trapped)
View all literature mentionsThis polyclonal targets Total glutathione (aldehyde-trapped): GSH+GSSG.
View all literature mentionsThis polyclonal targets taurine (aldehyde-trapped)
View all literature mentions